Real-World Treatment Patterns, Clinical Outcomes, Healthcare Resource Utilization, and Costs in Advanced Hepatocellular Carcinoma in Ontario, Canada.

The therapeutic landscape for aHCC has evolved in recent years, necessitating a comprehensive analysis of treatment patterns, clinical outcomes, HCRU, and costs to contextualize emerging treatments. This study aimed to investigate these outcomes using real-world data from Ontario, Canada. This retrospective cohort study was conducted using linked administrative databases from April 2010 to March 2020. Patients diagnosed with aHCC were included, and their clinical and demographic characteristics were analyzed, as well as treatment patterns, survival, HCRU, and economic burden. Among 7322 identified patients, 802 aHCC patients met the eligibility criteria for inclusion in the study. Treatment subgroups included 1L systemic therapy (53.2%), other systemic treatments (4.5%), LRT (9.0%), and no treatment (33.3%). The median age was 66 years, and the majority were male (82%). The mOS for the entire cohort from diagnosis was 6.5 months. However, patients who received 1L systemic therapy had an mOS of 9.0 months, which was significantly higher than the other three subgroups. The mean cost per aHCC-treated patient was $49,640 CAD, with oral medications and inpatient hospitalizations as the largest cost drivers. The results underscore the need for the continuous evaluation and optimization of HCC management strategies in the era of evolving therapeutic options.

Adapting Health Technology Assessment agency standards for surrogate outcomes in early stage cancer trials: what needs to happen?

INTRODUCTION: An avalanche of early stage cancer clinical trials is coming. The majority of these solely use surrogate outcomes that have not been validated against a target outcome of interest (e.g. overall survival). Current HTA guidance on surrogate outcome validation are not methodologically or practically conducive to this scenario. AREAS COVERED: We provide a high-level overview of methods, approaches, and conceptual thinking for making better use of limited evidence within early stage cancer HTA submissions. We outline regulatory and HTA issues and emphasize how evidence transitions from one to another, what major gaps currently exist, and how these may be bridged. We summarize current methodologies and practices, their pros and cons. We outline how complementary measurements strengthen evaluations and address fallacies and biases of conventional statistical methods for surrogate outcomes validation. The value of real-world data to support some of the necessary validity components is discussed. Lastly, we address the importance of the patient voice for better understanding which surrogate outcomes may appropriately inform HTA. EXPERT OPINION: Conventional surrogate outcome validation represents a fraught and sub-optimal framework for HTA purposes, particularly for early stage cancer. Tools for optimizing use of limited evidence exist. Education of stakeholders is highly needed.

Real-world treatment patterns and survival outcomes for treated biliary tract cancer patients using administrative databases in Ontario.

Background: There are limited data available on treatment patterns and outcomes of biliary tract cancers (BTCs) in Canada. The aim of this study was to understand treatment patterns, survival outcomes and healthcare resource use of BTC patients in Ontario, Canada. Methods: We conducted a retrospective population-level study using administrative data of patients diagnosed with advanced or metastatic BTC between January 1, 2010 and December 31, 2019. Results: A total of 2,142 BTC patients were identified; 702 (32.8%) with intrahepatic cholangiocarcinoma, 688 (32.1%) with extrahepatic cholangiocarcinoma, 363 (16.9%) with gallbladder cancer, 174 (8.1%) with ampulla of Vater cancer, and 215 (10.0%) with other types of BTC. In total, 1,314 patients (61.3%) were recurrent cases, and 828 (38.7%) were diagnosed with de novo advanced disease. A total of 1,727 patients (80.6%) received first-line systemic treatment of cisplatin plus gemcitabine (75.2%), FOLFOX [5-fluorouracil (5-FU), folinic acid (FA), and oxaliplatin] or FOLFIRI (5-FU, FA, and irinotecan) (11.5%), carboplatin plus gemcitabine (7.6%), or gemcitabine plus taxane (5.7%). Five hundred and twelve patients (29.6%) went on to receive a second-line treatment. Mean and median overall survival from diagnosis was 20.6 and 11.0 months, respectively. Mean and median overall survival from diagnosis was much higher among patients who received a systemic treatment at 23.8 and 14.1 months, respectively compared to 7.0 and 3.3 months, respectively for untreated patients (P<0.0001). Conclusions: Platinum and gemcitabine combinations are the most common first-line treatments. However, only a small proportion of patients go on to receive subsequent treatments. Survival in treated patients is higher than that in untreated patients. Our findings highlight the unmet need for effective systemic therapies for BTC.

Real-world treatment patterns, clinical outcomes, and health care resource utilization in advanced unresectable hepatocellular carcinoma.

BACKGROUND: The incidence of advanced unresectable hepatocellular carcinoma (HCC) is increasing in developed countries and the prognosis of advanced HCC remains poor. Real-world evidence of treatment patterns and outcomes can highlight the unmet clinical need. METHODS: We conducted a retrospective population-based cohort study of patients with advanced unresectable HCC diagnosed in Alberta, Canada (2008-2018) using electronic medical records and administrative claims data. A chart review was conducted on patients treated with systemic therapy to capture additional information related to treatment. RESULTS: A total of 1,297 advanced HCC patients were included of whom 555 (42.8%) were recurrent cases and the remainder were unresectable at diagnosis. Median age at diagnosis was 64 (range 21-94) years and 82.1% were men. Only 274 patients (21.1%) received first-line systemic therapy and, of those, 32 patients (11.7%) initiated second-line therapy. Nearly all of the patients received sorafenib (>96.4%) in first-line, and these patients had considerably higher median survival (12.23 months; 95% CI 10.72-14.10) compared with patients not treated with systemic therapy (2.66 months; 95% CI 2.33-3.12; log-rank p <0.001). Among patients treated with systemic therapy, overall survival was higher for recurrent cases, patients with Child-Pugh A functional status, and patients with HCV or multiple known HCC risk factors (p <0.05). CONCLUSIONS: In a Canadian real-world setting, patients who received systemic therapy had greater survival than those who did not, but outcomes were universally poor. These results underscore the need for effective front-line therapeutic options.